Effects of amiodarone and desethylamiodarone on rabbit myocardial beta-adrenoceptors and serum thyroid hormones--absence of relationship to serum and myocardial drug concentrations.

The antiadrenergic actions of amiodarone (Am) are well known but its effect and that of its metabolite, desethylamiodarone (DAm), on beta-receptor density (Bmax) and affinity (KD) are poorly defined. Thus, the acute and chronic effects of Am and DAm on myocardial beta-receptors in rabbits were determined relative to changes in thyroid hormones and serum and tissue drug concentrations. Bmax and KD were measured by radio-ligand binding, thyroid hormones by RIA, and drug levels by HPLC. Compared with controls, intravenous Am (20 mg/kg) reduced Bmax by 23% (p less than 0.05) and DAm (20 mg/kg) by 32% (p less than 0.05). After 3 weeks of chronic drug, the corresponding value for Am was 24% (p less than 0.05) versus 45% (p less than 0.05) for DAm. The effect of DAm was significantly greater (p less than 0.05) than that of Am, being comparable to that of Am (-44%) after 6 weeks. In the case of Am, doubling the dose (and myocardial level) led to no further decrease in Bmax. DAm also reduced Bmax more following chronic treatment than after acute administration (-45 versus -32%), a difference of borderline significance. Following 3 weeks of p.o. Am, T3 decreased 3% (NS) and reverse T3 (rT3) increased 90% (p less than 0.05); after 6 weeks, the corresponding values were 25% (p less than 0.05) and 181% (p less than 0.01). After 1 week of p.o. DAm, T3 did not change but rT3 increased by 34% (p less than 0.05); after 3 weeks the corresponding values were 21% (p less than 0.01) and 64% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)